Calcium and integrin-binding protein 1 (CIB1)
The protein contains 191 amino acids for an estimated molecular weight of 21703 Da.
Calcium-binding protein that plays a role in the regulation of numerous cellular processes, such as cell differentiation, cell division, cell proliferation, cell migration, thrombosis, angiogenesis, cardiac hypertrophy and apoptosis. Involved in bone marrow megakaryocyte differentiation by negatively regulating thrombopoietin-mediated signaling pathway. Participates in the endomitotic cell cycle of megakaryocyte, a form of mitosis in which both karyokinesis and cytokinesis are interrupted. Plays a role in integrin signaling by negatively regulating alpha-IIb/beta3 activation in thrombin-stimulated megakaryocytes preventing platelet aggregation. Up-regulates PTK2/FAK1 activity, and is also needed for the recruitment of PTK2/FAK1 to focal adhesions; it thus appears to play an important role in focal adhesion formation. Positively regulates cell migration on fibronectin in a CDC42-dependent manner, the effect being negatively regulated by PAK1. Functions as a negative regulator of stress activated MAP kinase (MAPK) signaling pathways. Down-regulates inositol 1,4,5-trisphosphate receptor-dependent calcium signaling. Involved in sphingosine kinase SPHK1 translocation to the plasma membrane in a N-myristoylation-dependent manner preventing TNF-alpha-induced apoptosis. Regulates serine/threonine-protein kinase PLK3 activity for proper completion of cell division progression. Plays a role in microtubule (MT) dynamics during neuronal development; disrupts the MT depolymerization acti (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| dbSNP:rs3210935 | |
| dbSNP:rs11551250 |
Biological Process
Angiogenesis
Apoptotic process
Cell adhesion
Cell division
Cellular response to DNA damage stimulus
Cellular response to growth factor stimulus
Cellular response to nerve growth factor stimulus
Cellular response to tumor necrosis factor
Cytoplasmic microtubule organization
Double-strand break repair
Endomitotic cell cycle
Extrinsic apoptotic signaling pathway
Negative regulation of apoptotic process
Negative regulation of cell population proliferation
Negative regulation of megakaryocyte differentiation
Negative regulation of microtubule depolymerization
Negative regulation of neuron projection development
Negative regulation of protein kinase B signaling
Negative regulation of protein phosphorylation
Platelet formation
Positive regulation of calcineurin-NFAT signaling cascade
Positive regulation of catalytic activity
Positive regulation of cell adhesion mediated by integrin
Positive regulation of cell growth
Positive regulation of cell migration
Positive regulation of cell migration involved in sprouting angiogenesis
Positive regulation of cell population proliferation
Positive regulation of cell-matrix adhesion
Positive regulation of ERK1 and ERK2 cascade
Positive regulation of establishment of protein localization to plasma membrane
Positive regulation of male germ cell proliferation
Positive regulation of NF-kappaB transcription factor activity
Positive regulation of protein localization to plasma membrane
Positive regulation of protein phosphorylation
Positive regulation of protein serine/threonine kinase activity
Positive regulation of protein targeting to membrane
Positive regulation of substrate adhesion-dependent cell spreading
Regulation of cell division
Regulation of cell population proliferation
Response to ischemia
Spermatid development
Thrombopoietin-mediated signaling pathway
Cellular Component
Apical plasma membrane
Axon
Cell periphery
Centrosome
Cytoplasm
Dendrite
Endoplasmic reticulum
Extracellular exosome
Filopodium tip
Golgi apparatus
Growth cone
Lamellipodium
Membrane
Neuron projection
Neuronal cell body
Nucleoplasm
Nucleus
Perikaryon
Perinuclear region of cytoplasm
Plasma membrane
Ruffle membrane
Sarcolemma
Vesicle
The reference OMIM entry for this protein is 602293
Calcium- and integrin-binding protein 1; cib1
Cib
Kinase-interacting protein 1; kip1
Kip
CLONING
Integrin-alpha-IIb-beta-3 (see 607759 and 173470), the platelet fibrinogen receptor, is converted from an inactive conformation to an active, high-affinity state through a mechanism that may involve the binding of proteins to the integrin cytoplasmic domains. To identify candidate proteins that bind to the cytoplasmic domain of alpha-IIb, Naik et al. (1997) screened a human fetal liver cDNA library using the yeast 2-hybrid system. They isolated a novel cDNA that encodes a predicted hydrophilic 191-amino acid protein that they called CIB. CIB contains 2 calcium-binding EF-hand motifs and shares 58% and 55% amino acid sequence similarity with calcineurin B (601302) and calmodulin (114180), respectively. Using RT-PCR and Western blot analysis, Naik et al. (1997) detected CIB mRNA and CIB protein, respectively, in platelets. Gentry et al. (2005) stated that the CIB1 protein contains 10 helical domains separated from one another by loop regions. Gel filtration and sedimentation equilibrium analyses showed that only a small percentage of CIB1 formed dimers, with most CIB1 remaining monomeric in the presence or absence of Ca(2+). The calculated molecular mass of CIB1 is 21.7 kD, but the protein had an apparent molecular mass of either 26.9 or 30.6 kD, depending on the method used, most likely due to its irregular shape. Using Western blotting and immunohistochemistry to analyze heart Cib1 expression in vivo in mice, Heineke et al. (2010) observed high levels at embryonic day 16, at birth, and 1 week after birth, with a progressive reduction in expression with aging. Localization of Cib1 within cardiac myocytes shifted from a diffuse cytoplasmic pattern before birth to the sarcolemma in the adult heart. CIB1 was also detected at the sarcolemma in histologic sections from human hearts, with more CIB1 at the sarcolemma in sections from hypertrophic human hearts than control hearts.MAPPING
By PCR analysis of human/rodent somatic cell hybrid and radiation hybrid panels and FISH, Seki et al. (1998) mapped the KIP gene to chromosome 15q25.3-q26.1.GENE FUNCTION
By yeast 2-hybrid analysis, Naik et al. (1997) found that CIB bound specifically to the alpha-IIb cytoplasmic domain and did not interact with the cytoplasmic domains of the other integrin subunits examined. CIB specifically bound calcium in blot overlay assays. Naik et al. (1997) demonstrated an in vitro interaction between CIB and intact integrin alpha-IIb-beta-3 using enzyme-linked immunosorbent assays. They suggested that CIB is a candidate regulatory molecule for integrin alpha-IIb-beta-3. Heineke et al. (2010) identified CIB1 in a screen for previously unknown regulators of cardiac hypertrophy, and yeast 2-hybrid screening revealed calcineurin B (601302) as a CIB1-interacting partner. Studies in Cib1 -/- mouse hearts showed that Cib1 anchors calcineurin to the sarcolemma and controls its activation in coordination with the L-type Ca(2+) channel. Immunohistochemical analysis demonstrated that Cib1 protein amounts and membrane association were enhanced in cardiac pathologic hypertrophy, but not in physiologic hypertrophy in mice. Consistent with these observations, Cib1-deleted mice showed a marked reduction in myocardial hypertrophy, fibrosis, cardiac dysfunction, and calcineurin-NFAT (NFATC; 600489) activity after pressure overload, whereas the degree of physiologic hypertrophy after swimming exercise was not altered. Transgenic mice with inducib ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602293 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed